1. Field of Invention
This invention relates to preventing and treating skin and nail infections using germicidal radiation to inactivate and kill organisms that cause such infections.
2. Background of the Invention
The germicidal effects of certain types of light have been recognized for many years. As early as the late 1890's certain types of ultraviolet light were found to have a germicidal effect. However, the wavelengths of light found to be germicidal have very little power to penetrate which limited their usefulness in treating infections. The most germicidal band, labeled UVC and extending from 240 to 280 nm, is totally absorbed by the atmosphere before it reaches the Earth's surface. Published research indicates that UVC can only penetrate the skin about 0.1 mm. Although germicidal light was found useful to sterilize air or water and to treat hard surfaces such as laboratory benches, its lack of penetration made it appear unsuitable to treat skin and nail infections.
Niels Finsen received the 1903 Nobel Prize in Medicine for his discovery that light in the ultraviolet region could be used to treat skin tuberculosis, a very serious disease at that time. The treatment as described in the 1903 Nobel Prize acceptance speech consisted of concentrating the rays of the sun and eliminating its longer heat producing rays or using a carbon arc lamp. The skin is exposed for an hour or so until it becomes red and inflamed. This treatment was repeated as necessary until the skin scarred over and then later grew in clear. The treatment was described as having no unpleasant effects, but was expensive, and required constant supervision. The light used had a very low percentage of UVC and it was thought that the main effect of the light used was to stimulate the body's natural defenses. It was thought that germicidal light could not effectively penetrate the skin to treat the infection but that the main purpose of the light was to stimulate the body's natural defenses.
This type of treatment for skin tuberculosis and several other skin diseases continued through the 1950's but was eventually replaced by the use of antibiotics. Early use of ultraviolet light was much more of an art than a science. In the early 1900's science was just beginning to form its modern theory of the composition of light and the science of genetics was many decades off. Thus researchers did not have the theoretical knowledge of how germicidal light damages genetic material to guide them in their treatments.
Early practitioners of phototherapy for the treatment of skin infections were aware of the germicidal effects of light but did not think they contributed significantly to UV phototherapy. In Ultra-Violet Radiation and Actinotherapy (Russel, 1933) it was noted that ‘Ultraviolet light is absorbed by the protoplasm of the organism, and in a culture, or on the surface of a wound, one bacterium will protect a second lying under it; so in a lesion like lupus very little beneficial therapeutic effect can be considered to be due to the bactericidal effects of the rays. It is due rather to the increased lymphocytosis in the part, and stimulation of cicatrisation.’ (Russel, 1933, pg. 288). The text also notes that ‘the absorption by the skin of very short wave-length, is very great, all rays shorter than 3000 angstroms [300 nm] being absorbed by a later of epidermis 0.1 mm in thickness’ (Russel, 1933, pg. 272-273). The lamps which were used to treat skin infections had at least 95% of their energy emitted at wavelengths over 300 nm and thus had very little energy in wavelengths considered germicidal. This compares to modern low pressure mercury germicidal lamps where 95% of light is emitted at 254 nm—almost the exact opposite of earlier lamps used to treat skin disorders.
U.S. Pat. No. 1,856,969 by Reiter and Gabor in 1932 describes a type of phototherapy to modulate living tissue that was used as part of empirically based treatment of skin disorders. The patent describes the use of UV to stimulate the natural defenses of the body and includes a filter to prevent light less than 320 nm from reaching the skin since light below 320 nm was felt to be detrimental to treatment. This patent illustrates that most early UV therapy was focused on the stimulating effects of UV and not on its germicidal qualities since the wavelengths considered germicidal (less than 315 nm) were considered to be detrimental to treatment.
Treatment of skin diseases continued on an empirical basis through the 1950's with a multiplicity of units being produced each with different approximated guidelines of how to best use them for various disorders and infections. The empirical basis of treatment of these disorders was based on judiciously applying ultraviolet light to cause erythema (redness) to develop. The treatment was then adjusted to bring about various degrees of sunburn depending on the disorder being treated. Mild erythema (slight redness) was assigned a value of E-1 while the most sever erythema (blistering and third degree burns) was assigned an E-4. The most serious infections often merited a treatment bringing about an E-4 erythema for a sustained period. The induced erythema was thought to stimulate the body's defenses, particularly increasing the bactericidal ability of the blood. Although this was the most prevalent theory of why this treatment was efficacious there was no absolute consensus. The lack of consensus with regard to how this type of treatment worked and the large number of lamps that were being marketed in the first half of the twentieth century was probably bewildering to many doctors. Nevertheless, in the absence of modern antibiotics, even the empirical use of ultraviolet light to treat skin infections.
Electrotherapy and Actinotherapy; A Textbook for Student Physiotherapists authored by E. B. Clayton and published in 1952 (2nd edition) shows of the state of the art of phototherapy before use of modern antibiotics caused this form of treatment to lose favor. This 451 page textbook covers all aspects of phototherapy beginning with the theory, the type of equipment used, and treatment of various types including skin disorders. Portions of the treatment section for skin tuberculosis read as follows, “The Finsen-Lomholt water cooled carbon arc or the Kromayer lamp is employed. The latter has the disadvantage that its spectrum includes a quantity of abiotic rays which are not required and merely increase the superficial inflammation . . . . The initial exposure is commonly five times a fourth degree erythema.” (pgs. 413-414). This extract of the book notes that abiotic (germicidal) light is not considered helpful for treatment. It also shows that dosages for treatment were based on empirically derived rules of thumb related to how severe the produced erythema was. Although almost 100 pages are devoted to describing various treatments there is no mention of dosage in terms of the amount of energy applied nor is there mention of any specific wavelengths.
Empirical use of ultraviolet light had a number of undesirable side effects including a wide spectrum of light including high amounts of UVB light now known to be carcinogenic. The relative amount of germicidal light was extremely low which made any possible benefit due to its inclusion very small and probably undetectable. Also, the cure rate was also much lower than can be expected with a well understood theory of how germicidal light inactivates organisms. Thus, when safer and more effective antibiotics were introduced in the 1950's the practice of empirically using ultraviolet light to treat skin infections was quickly abandoned by the medical profession in general. While ultraviolet light may still be used to empirically treat skin infections in isolated areas of the world its general use has been abandoned.
There appears to have been no application of the recent advances in genetics, air handling, and water and wastewater disinfection to transform the use of germicidal light to scientifically treat skin infections. The present invention combines these advances in other fields to develop a novel and unique approach to scientifically treat skin and nail infections in a manner that increases the efficacy of treatment while minimizes the side effects of such treatments.
It should be noted that there is no indication that this type of treatment was ever applied to treating nails. While the text discuss a number of different disorders affecting different parts of the body (including skin, nose, throat, anus, etc.) the mention of nails is not found in any text. This is understandable given the limited ability of nails to transmit light in the ultraviolet range and the fact that nail diseases in general are less life threatening than skin infections.
With the discovery of DNA and RNA in the 1950's and the subsequent development of the science of genetics, scientists discovered that each cell contained a highly sophisticated code to permit the cell to reproduce. Later, it was found that certain kinds of ultraviolet light could damage this genetic material and prevent a cell from reproducing. This knowledge was applied in many different fields including water and wastewater treatment (where it was used to disinfect water), to sterilize surfaces, and to sterilize air. However, it was not applied to treat skin infections. This was perhaps due to several reasons including the following:                The widespread knowledge that UV cannot penetrate deeply made it a less than ideal candidate to treat an infection that may not be totally on the surface of the skin. Since it is well documented that light less than 300 nm cannot penetrate below the first 0.1 mm of the epidermis, its penetrating power was thought insufficient to treat infections.        The old empirical use of UV light made use of lights of varying characteristics and strengths. It is likely that these lights cause some pain and tenderness due to their non-specificity. Also, since there was no knowledge of how the light cleared infections, it was applied in a broad manner and probably had significant side effects due to overdosing including cancer due to high level of carcinogenic UVB.        
While Niels Finsen is cited as the founder of phototherapy by many authors, the industry has all but abandoned the use of ultraviolet light to treat infections and has instead concentrated on the visible and infrared part of the spectrum from 400 nm to 1000 nm. The invention disclosed in this application builds on Finsen's work and extends it in new and innovative ways by combining new knowledge of genetics and advances in the use of ultraviolet light to disinfect air and water. The combination of diverse knowledge that the invention builds on is not generally known to those skilled in the art of phototherapy and when this new knowledge is combined with the existing empirical base provided by Finsen and other early phototherapists, new and unobvious applications of this knowledge to prevent and treat skin and nail infections emerge.
The germicidal effects of electromagnetic radiation have been recognized for many years. Currently, germicidal radiation (also called germicidal light) is being used more frequently at water and wastewater treatment plants to render water-borne pathogens harmless. Additionally, germicidal light is used to sterilize and purify air, particularly in laboratories and medical establishments. It is also used to sterilize equipment at such establishments. Germicidal light has been used for several years to sterilize and disinfect food products and has also been used to sanitize the hands to prevent the spread of germs to other persons. Over the years a large body of knowledge concerning germicidal radiation has been developed but has not been systematically applied to address important problems with respect to treating skin and nail infections.
While germicidal light is not used by itself to treat skin and nail infections, certain types of light that are considered non-germicidal are frequently combined with other additional chemical compositions to treat existing psoriasis, rashes, and other non-infectious skin disorders. It is believed that this type of treatment, termed phototherapy, is effective because it has an immunosuppressive effect that permits the body to heal itself. Recently, lasers alone have been successfully used to treat psoriasis by clearing localized chronic plaque. Phototherapy is also used to treat jaundice which is also a non-infectious disorder. However, no method of using germicidal light alone has been discovered to successfully treat existing microbial infections nor has this type of light been used as a preventative treatment for infections.
Perceived Inability of Germicidal Light to Penetrate Skin and Nails
The main reason that germicidal light alone has not been used to prevent and treat skin and nail infections is that the most potent germicidal light is in the UVC range (240 nm to 300 nm) and this type of light cannot penetrate the skin and nails deeply. Significantly less than 1% of UVC light can penetrate nails or the deeper than 0.1 mm of skin (i.e. does not penetrate the epidermis).
UVB (280 nm 315 nm) while not generally considered germicidal also has some limited germicidal ability particularly in the 280 nm to 300 nm part of the spectrum. However, it also has limited penetrability. For example UVB it is estimated that less than 5% of light at 315 nm penetrates the epidermis (approx. 0.125 mm deep) or nails. The perceived inability of germicidal light to penetrate the skin and nails is one of the major reasons that this type of light has not been used to prevent and treat infections. If the light cannot penetrate skin or nails and reach the infectious organisms it is of no use for treating infections. However, it is this difference between no penetration and little penetration that the disclosed invention makes innovative and unobvious use of. Although less than 1% of UVC light can penetrate nails or can penetrate skin deeper than 100 mm, the less than 1% of light that is able to penetrate deeper is sufficient to prevent and treat skin and nail infections when applied properly.
Less than 8% of UVB at 315 mm can penetrate nails or skin deeper than 0.1 mm. This is much greater than the penetration ability of UVC, however, given its lower germicidal ability it does not appear to be as effective treatment for infections. Nevertheless, UVB can be used germicidally to treat infections if it is of sufficient strength or if it is accompanied by use of UVC light.
There is a large amount of literature that teaches that germicidal light cannot penetrate well. The Physics Society in its July 1998 paper titled “Ultraviolet Radiation and the Public Health” notes that “UVC, used in germicidal lamps, causes almost no damage because of its low penetration of the skin.” INTERSUN, the global UV project sponsored by the United Nations indicates only 5% of UVC (at 254 nm) can penetrate to approximately a quarter of the depth of the epidermis and less than 1% can penetrate more than half the depth of the epidermis. Many other sources indicate that UVC cannot penetrate the skin or can do so only to a very limited depth. However, this depth is sufficient to treat infections since organisms are particularly susceptible to germicidal radiation. Also, with respect to nail infections, the additional radiation required to penetrate the nail is not harmful to the nail since it is composed of dead keratin.
UVC Dose Necessary to Inactivate Microbes
A second major reason the use of UV has not been contemplated are the relatively high doses necessary to kill some types of organisms. However, it has been found that it is not always necessary to kill organisms to render them harmless. It has been shown that organisms can be inactivated and rendered harmless using far less radiation than is necessary to kill them completely. Therefore, although its use as a treatment for has been overlooked in the past, electromagnetic radiation of sufficient strength can be used to treat human and animal infections.
There are several publications that note that organisms can be rendered harmless with less energy than is necessary to kill them. The inactivation of organisms by damaging RNA and DNA and preventing them from reproducing is a method used for disinfection of highly transparent potable water and is discussed in more detail in U.S. Pat. No. 6,129,893 to Bolton. The patent describes a method for preventing the replication of Cryptosporidium parvum using ultraviolet light. This patent indicates that ultraviolet light can inactivate bacteria (as measured by infectivity studies) at doses that are 3% to 10% of the dose necessary to actually kill the organisms (as measured by microscopic examination of ruptured membranes). The method of inactivation is described as damage to the DNA and RNA that prevents the organisms from replicating. Since organisms are not long-lived in themselves, they are unable to continue to cause infection if they are unable to replicate. This discovery is applied to the inactivation of a pathogen in drinking water to render it safe for consumption. However, the method is only to irradiate one type of organism and then only in highly transparent drinking water.
The EPA guidance manual on Alternate Disinfectants and Oxidants (April 1999) devotes Chapter 8 to a discussion of germicidal UV as a disinfectant for drinking water. The manual notes that a UV wavelength of 240 to 280 nm is highly absorbed by the RNA and DNA of a microorganism. The absorbance of UV by the organisms results in the damage to the organism's ability to reproduce. The damage is often caused by the dimerization of pyrimidine molecules. A dimer is a molecule consisting of two identical simpler molecules and dimerization is the process of linking the two molecules together. Dimerization of the pyrimidine molecules distorts the DNA helical structure. The EPA guidance manual also notes that the dose to inactivate 90% of most types of organisms is very low with a typical range of 2 to 6 mJ/cm2. The manual notes that the germicidal radiation can be generated by a number of sources including a low pressure mercury lamp emitting at 254 nm, a medium pressure lamp emitting at 180 to 1370 nm, or lamps that emit at other wavelengths in a high intensity pulsed manner.
It should also be noted that it is not necessary to kill and inactivate all organisms in order to effect a cure for an infection. If a substantial amount of the organisms that have caused an infection are destroyed or rendered inactivated, the body's natural defenses will often work to clear the infection. Thus, doses of radiation necessary to effect a cure for an infection may be much lower than those necessary to sterilize an area by total destruction of all organisms.
While germicidal light is often said to inactivate organisms by damaging their genetic material and preventing them from reproducing, germicidal light can be applied in higher dosages to damage enough of the genetic material in the cell and prevent it from being able to properly function, thus leading to its death. For example, mRNA (messenger RNA) is used to control cellular processes, however, if it is severely damaged it cannot perform this function.
UVB as Germicidal Light
While UVB light has some germicidal qualities it is not often used to inactivate or kill organisms. Although approximately 10 times more UVB light can penetrate a given depth of skin and nails than UVC light, its lower germicidal ability does not make it as attractive a choice. UVB is also considered the band of UV that causes the most damage to skin, and is therefore considered more carcinogenic, and is thus avoided where possible. Additionally, UVB light is more difficult to generate than UVC light which is easily produced by a mercury vapor light (which is similar in manufacture to a fluorescent light). Nevertheless, UVB can be used germicidally and it may be desirable to use it particularly in conjunction with UVC light. The portion of the UVB range that adjoins the UVC range (UVB between 280 nm and 300 nm) is almost as germicidal as some bands of UVC. Practitioners of photobiology sometimes term UV light between 200 nm and 300 nm as ‘Far UV’ light (as opposed to ‘Near UV’ light which is often listed in the range of 300 to 400 nm). The current invention makes use of UVB for treatment of skin and nail infections even though most literature ignores its germicidal ability and teaches that UVB does not penetrate deeply. The invention also encompasses Near UV light in the range of 200 nm to 300 nm due to its germicidal nature.
Other Types of Germicidal Radiation
U.S. Pat. No. 5,900,211 shows that it is not only UVC and UVB that can be used to sterilize water and food. Dunn discusses the use of pulsed polychromatic light to inactivate organisms. Dunn uses much lower amounts of energy to inactivate an organism than would be necessary to destroy it by excessive heat. However, Dunn applies this technology only to the sterilization of food and other materials and does not contemplate it for treatment of skin or nail infections. This is presumably because of the perceived inability of the light to penetrate the skin or nails. (Dunn indicates that the effectiveness of the light is dependent on its ability to penetrate a medium effectively.)
Prior Art Using UVC to Kill and Inactivate Organisms
U.S. Pat. No. 6,254,625 shows an apparatus to sterilize hands to prevent the spread of infectious organisms. This apparatus makes use of light to sanitize the surface of the hands to prevent infections from spreading form person to person. In all of its embodiments it consists of at least two items. It makes use of light to kill organisms along with either additional light to recuperatively heal the skin that has been irradiated or the use of ozone to increase the efficiency of killing organisms. The recuperative healing light uses the phenomenon of photoreactivation whereby cells and organisms that have been damaged can repair the damage using such light of a different wavelength. The inclusion of this source of light as part of the apparatus indicates that the disease causing organisms are killed and not merely inactivated otherwise they too could repair damage by photoreactivation. Additionally, the patent does not contemplate the use of the apparatus to treat an infected area of the skin and it makes no mention of treating any infection of the nails using electromagnetic radiation. The apparatus relies on the use of ozone to kill any organisms under the nails or shielded by debris and notes incorrectly that UVC radiation will not penetrate the nail. Rosenthal appears to be unaware that germicidal UV can penetrate the skin and nails and is used to treat infections.
U.S. Pat. No. 6,283,986 discusses the use of UVC radiation to treat wounds. However, Johnson only applies radiation to open wounds, which can be readily exposed, and notes that “given the short wavelength of UVC, no penetration of the underlying tissue would be expected.” The patent makes no mention of skin infections and mention of the nails is totally absent from the application although nail infections comprise a large part of total dermal infections. Possibly, the reason the patent only applies to wounds is that by their nature wounds are open and therefore capable of having their surfaces irradiated. It appears that Johnson is also unaware of the ability of germicidal radiation to penetrate the skin and nails.
It is the misconception that germicidal light cannot penetrate skin and nails which has in part prevented the discovery that germicidal radiation, including UVC, can indeed penetrate to a depth sufficient to be used successfully to treat skin and nail infections. While it is true that skin and nails will absorb a large percentage of UVC, enough can penetrate to successfully treat and prevent infections.
Nail Infections and Treatment
Nail infections are a particularly significant problem in the general population, affecting an estimated 5% to 15% of the overall population (approximately 15 to 45 million people). This percentage is significantly higher in the elderly age group and among athletes and other individuals who have high moisture in the area of their feet. Nail infections are often caused by fungus and this type of infection is termed onychomycosis. Currently, the preferred method for the prevention and treatment of skin and nail infections relies on application of topical medications or ingestion of medications. These medications are used to treat an existing infection, not for the prevention of an infection. Cost of treatment using medication can be between $600 and $1200 per course of treatment and can last three to six months. This is the amount of time it takes the medication to be incorporated into the nails. Another one to six months is then required for the nail to become free of infection. It should be noted that the cost noted above does not take into account doctors visits or diagnostic testing to determine if the patient can tolerate the medication (many medications can cause liver and other damage).
The problems associated with oral anti-fungal medications can be illustrated by several quotes from the clinical testing results for Itraconazole capsules (marketed under the trademark name SPORANOX® manufactured by Janssen Pharmaceutica, Inc.) which was the most prescribed anti-fungal in the U.S. in 1996. The success rate for treatment of onychomycosis of the toenail is reported as follows—“Results of these studies demonstrated mycological cure . . . in 54% of the patients. Thirty-five (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycological cure (clearance of all signs, with or without residual nail deformity).” With respect to adverse reactions—“SPORANOX® has been associated with rare cases of serious hepatoxicity, including liver failure and death. Some of the cases had neither pre-existing liver disease nor a serious underlying medical condition.” In a study of 602 patients treated for systemic fungal disease, “treatment was discontinued in 10.5% of the patients due to adverse events.”
Although it is relatively rare, death is another serious side effect of oral antifungal medications. The two most popular antifungal medications used to treat nail infections were implicated in a total of 35 deaths in the U.S. between 1996 and 2001. This caused the FDA to issue a health advisory for these medications in May of 2001.
Although the currently preferred method of treating nail infections is the use of oral medication, there are several other treatments in use. There are several topical applications that are used to treat fungal infections of the nails. However, these have an even poorer success rate than oral medications and the infections tend to re-occur.
U.S. Pat. No. 6,090,788 to Lurie shows destruction of fungal infections of the nails by introducing a pigment into an infected area and then heating the pigment in the infected area with a laser in order to raise the temperature high enough to kill the organisms that have caused the infection by excessive heating. The energy listed in the preferred embodiments is from 5 to 15 J/cm2 and it has a relatively long wavelength (generally 500 to 700 nm) in order to penetrate the nail. The high amount of energy and long wavelength of light is great enough to cause excessive heating of the surrounding area thus destroying the organism. However, such high energy levels also have undesirable effects on the surrounding tissue such as redness and swelling.
Lurie incorrectly notes that typical fungi do not have pigment and, therefore, cannot absorb light. However, the fact is that all cells will absorb light at a wavelength of between 240 and 280 nm since the DNA in the organism will absorb light at this wavelength. Also, Lurie is not cognizant of the fact that organisms can be inactivated at much lower doses than those necessary to destroy them by excessive heat. Due to the complicated nature of the treatment, U.S. Pat. No. 6,090,788 is proposed as a method to treat an infection, not to prevent one.
Lurie also notes that the light he uses for treatment must easily penetrate the skin which is something that UV does not do. Thus it would not be a natural extension of Lurie's treatment to use UV light to directly treat nail infections.
Lurie notes “there is a widely recognized need for, and it would be highly advantageous to have, a phototherapy method for treating skin and nail pathogens and a pharmaceutical composition to effect same.” It may be added that there is even a greater need to treat skin and nail infections using germicidal radiation only, particularly if said radiation could be effective at a much lower dose and not have the side effects associated with high energy lasers.